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Elsa AACN > Ch 18 Chromosomal and Genetic Syndromes > Flashcards

Ch 18 Chromosomal and Genetic Syndromes Flashcards

1
Q

Definition of Neurofibromatosis Type 1

A

skin and bone abnormalities resulting from tumors growing along the nerves

affects CNS and skin

most common of all types of neurofibromatoses

do not recover from NF1

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2
Q

Neurofibromatosis Type 2

A

bilateral acoustic schwannomas on the CN 8
meningioma
ependymoma

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3
Q

schwannomatosis

A

rare form of neurofibromatosis (NF) that causes multiple nerve sheath tumors called schwannomas.

Chronic pain

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4
Q

diagnostic criteria of NF1

A

6 or more cafe au lait macules

  • > 5mm in perpibertal people or >15mm in postpubertal people
  • 2+ neurofibromas OR 1 plexiform neurofibroma
  • freckling in axilla or groin
  • optic glioma
  • 2+ lisch nodules
  • distinctive bonylesion
  • 1st degree relative w/ NF1
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5
Q

neuropathology in NF

A
  1. brain tumor
  2. T2 hyperintensities
  3. Macrocephaly/megalencephaly - 30-50% of people
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6
Q

neuropathology in NF
- T2 hyperintensities
Seen in what population ? %?
Where does it occur?

A

T2 hyperintensities

  • seen in 60-70% of children
  • unidentified bright objects
  • occur in basal ganglia, cerebellum, thalamus, brainstem, subcortical WM
  • not associated with cognitive impairment
  • usually resolve by early adulthood
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7
Q

neuropathology in NF

- Macrocephaly/megalencephaly

A

Macrocephaly/megalencephaly - 30-50% of people

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8
Q 
neuropathology in NF1
- brain tumor
What % of people have it?
Present by what age 
What does it involve?
A

brain tumor

  • 15% of people with NF1
  • most present by 6 years
  • most are benign optic glioma
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9
Q

NF 1 Cognitive impairment

A 
Vs deficits one of the first cognitive deficits
30-65% with LD
30-50% ADHD
4-8% ID 
language deficits
motor skills
internalizing mood problems (but not huge risk for severe psych sx)
social difficulties

INTACT verbal and visual memory

deficits do not improve over time, but remain consistent or worsen

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10
Q

lifespan with NF1

A

50-60 years

mortality due to vascular dysplasia

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11
Q

Definition of Tuberous Sclerosis Complex (TSC)

A 
autosomally dominant 
neurocutaneous disorder
genetic disorder that causes tumors to form in many different organs, primarily in the brain, eyes, heart, kidney, skin and lungs
arise from one of 2 genes: TSC1 or TSC2
chromosome 9 and 16
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12
Q

Neuropathology of TSC

A
  1. cortical tuber
  2. subependymal nodules
  3. subependymal giant cell astrocytoma
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13
Q

Cortical tuber

A

potato like appearance of lesions
proliferation of glial and neuronal cells
loss of six layered structure of cortex

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14
Q

Subependymal nodules

A

form in walls of ventricles

may become subependymal giant cell astrocytoma (SEGA)

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15
Q

subependymal giant cell astrocytoma (SEGA)

A
  • slow glowing tumor
  • seen in children developed under 20 years
  • 5-20% of children
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16
Q

Dx/ problems associated with TSC

A

80-90% with epilepsy - begins in infancy, often intractible
45% ID
40-50% ASD
25-50% ADHD
increased risk for anxiety and depression
>50% behavioral problems (aggressive outburst, temper problems)
TAND

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17
Q

Life expectancy of TSC

A

depends on severity of symptoms

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18
Q

Treatment of TSC

A

no cure
use antiepiletic drugs for seizures
Everolimus (mTOR inhibitor) to tx SEGA and epilepsy
not good candidates for surgery because have multiple seizure foci

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19
Q

NP results for TSC

A

bimodal distribution of IQ (30% of profound ID, 70% near normal - 130)
LD in normal IQ
attention and EF deficits
memory recall deficit, recognition intact
TAND - Tuberous sclerosis associated neuropsychiatric disorders (psychsocial behavioral intellectual problems)

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20
Q

What is TAND

A

tuberous sclerosis associated neuropsychiatric disorder

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21
Q

Sturge Weber Syndrome (SWS)

A

neurocutaneous disorder

PFVG
port wine birthmark (PWB)
facial capillary malformation 
- usually affects face in region of ophthalmic division of trigeminal nerve
vascular malformation of the brain 
glaucoma
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22
Q

Gene location of SWS

A

somatic mosaic mutation in the GNAQ gene on 9q21

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23
Q

neuropathology of SWS

A

leptomeningeal angioma
cerebral atrophy
cortical calcification

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24
Q

leptomeningeal angioma

A
  • capillary venous vascular malformation of the brain
  • port wine birthmark increases brain involvement by 10-20%
  • bigger size birthmark increases risk
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25
Q

cerebral atrophy and cortical calcification in Sturge Weber syndrome

  • where is it usually seen?
  • one other characteristic
A

usually lateralized

seen in occipitoparietal regions

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26
Q

disorders and medical problems with SWS

A

seizures (typically begin in childhood)

  • 75% unilateral brain involvement have seizures
  • 95% bilateral brain involvement have seizures
  • seizures occur on the side of body contralateral of PWB

headaches and migraines

stroke like weakness contralateral of brain involvement

CNS problems when PWB involves upper division of trigeminal nerve

30-60% glaucoma

growth hormone deficiency 18x more likely

early onset dementia in 50s and 60s

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27
Q

Kids with SWS are more vulnerable to stroke like episodes precipitated by?

A

falls

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28
Q

Prognosis of SWS can be related to

A

age of onset of seizures

  • onset before age 6 months has worse prognosis
  • later seizure onset (after 9-12 mos), unilateral brain involvement usually have better outcome
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29
Q

Treatment of SWS

A

no cure
use of antileptic drugs to control seizurs
surgery (surgical lobectomy, hemispherectomy, callosotomy)
low dose aspirin (microvascular thrombosis)

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30
Q

NP results for SWS

A

few studies done with this population, no typical NP profile
60% with ID - LOW IQ!!
Learning problems
attention
processing speed slow
sensorimotor functions vary, and seen in stroke-like episodes
Vs skills also deficits
language comprehension, word list, verbal memory (L hemisphere)

disruptive behavior in children
anxiety in children
SUDs and depression in adults

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31
Q

Williams Syndome

A

facial dysmorphology (ELF - like!!)
connective tissue abnormality
cardiovascular disease
mild to mod cognitive deficits

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32
Q

Gene location of Williams syndrome

A

deletion of 26 to 28 genes on chromosome 7

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33
Q

neuropathology of Williams syndrome

A

reduction of cerebral volume with preservation of cerebellar volume (gray matter ok, reduced WM)
narrowing of corpus callosum
abnormal cell density in primary visual cortex
reduced sulcal depth in intraparietal occipitoparietal sulcus (VS deficits!)
abnormal neural pathway, amgydala activation when seeing threatening scenes and under activation when seeing threatening face
- hypersocial and anxious trait

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34
Q

medical disorders seen in Williams (5)

A

70% failure to thrive as infants
- motor delay and hypotonia as babies
atypical language development in sequence
50-75% cardiovascular disease - accounts for shortened lifespan
50% strabismus, cataracts, visual acuity problems
85-95% hypersensitivity to sounds

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35
Q

NP results in Williams

A 
average IQ = 55 (most of them are ID)
verbal IQ > non verbal IQ
VS deficit - HALLMARK!!
object and facial recognition in tact
50-60% ADHD
hypersocial, hyperfriendly, lack social judgment
anxiety
conversation sterotypies (open ended social situations ok, but no good in constrained social contexts)
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36
Q

Interesting characteristics about williams

A

Elf like
musical affinity
premature gray hair and wrinkling of skin
hoarse voice

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37
Q

22q11.s deletion syndrome AKA

A

DiGeorge syndrome
Shprintzen syndrome
Velocardio facial syndrome

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38
Q

22q11s deletion syndrome definition

A

multiple congenital anomalies

cardiac malformations
hypocalcemia
hearing loss (conductive)
palatal deficits

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39
Q

neuropathology of 22q11s

A

reduced total brain volume by 10% (white matter more reduced than gray matter)
frontal lobe volume ok
reduced parietal lobe volume
reduced cerebellar volume (vermis and pons)
reduced hippocampus
disorganized axonal tracts
cortical thinning in parietooccipital and orbitofrontal regions

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40
Q

other medical disorders in 22q11s

A

Medical
75-80% congenital heart defect - leads to mortality
69% palatal abnormality in speech and feeding

NP
82-100% LD
30-40% ADHD
10-30% ASD

Mood
30-40% anxiety, phobia, separation anxiety, OCD
20-30% mood disorders (MDD and Bipolar)
25-30% psychotic disorder

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41
Q

22q11s NP results

A

nonverbal before age 3
expressive < receptive language

IQ borderline
verbal > non verbal skills

NLD profile
deficits in facial memory
math difficulties (VS based only)

impaired attention and EF

strong rote memory
good decoding

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42
Q

22q11s has increased risk for

A

psychosis and schizophrenia (25x general population)

  • onset late teens to early 20s
  • does not respond well to antipsychotic meds
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43
Q

interesting things about 22q11s

A

bland affect

no facial expression

44
Q

Adrenoleukodystrophy (ALD)

A

X linked
recessive disorder affecting CNS myelin and adrenal cortex caused by defect in gene ABCD 1
degenerative
death within 2-5 years after onset

45
Q

males or females more likely to have ALD?

A

males, because x-linked disorder

46
Q

ALD neuropathology

A

inflammatory brain demyelination - posterior pattern in 80%, demyelination at corpus callosum, spread into parieto-occipital white matter
noninflammatory distal axonopathy - long tracts of spinal cord, AMN phenotype

47
Q

4 main phenotypes of ALD

A 
cerebral inflammatory
- childhood cerebral (CCALD) - CLASSIC TYPE 31-35%
- adolescent (AdolCALD)
- adult
AMN (adult onst)
- AMN no cerebral: slow progression
- AMN cerebral: rapid progression
Addison
asymptomatic
48
Q

CCALD onset features and age

A

3-8 years
first presenting like ADHD symptoms
then intellectual, behavioral, neurological declines
minimally responsive state within 2 years of onset, then DIE!!!

49
Q

AdolCALD

A 
progression slower than CCALD
adrenal insufficiency
neurological dysfx
psych sx
death within 1-2 years of onset
50
Q

ACALD

A

early cognitive decline
psych sx e.g. schizophrenia or psychosis
motor impairment
death within 3-4 years of onset

51
Q

Treatment of ALD

A

adrenal hormone replacement therapy to treat primary adrenocortical insufficiency
Lorenzo’s oil
hematopoietic stem cell transplant (HSTC)
- leads to improvement in nonverbal IQ
- good outcome
STEM cell - 68% 5-year survival rate from related donor

52
Q

NP results for ALD

A

non verbal deficits (VS)
EF deficits
attention problems seen in children first
psych sx seen in adults first
pattern seen in other demyelinating diseases such as MS

53
Q

Klinefelter syndrome 47 XXY

A 
most common sex chromosome aneuploidy ONLY in men
extra X chromosome
tall stature
hypogonadism
fertility problems
54
Q

Kleinfelter Diagnosis when?

A

10% prenatally, 25% childhood, 65% puberty

55
Q

neuropathology of klinefelter

A

reduced overall brain volume (limbic area, caudate nucleus, cerebellum)
enlarged ventricles
reduced temporal lobe gray matter volume
increased anomalous cerebral dominance (right ear advantage)
language less lateralized in men (more activity in R)

56
Q

Disorders in klienfelter

A 
35-65% ADHD
5-10% ASD
50-75% LD
mortality rate, loss of 2.1 years
increased rate for breast CA
57
Q

progression of Klinefelter

A

subtle in childhood, children with motor and speech delay
tall stature seen in adolescence usually
testosterone deficiency in puberty - slow pubertal development
no facial, pubic hair
microorchidism - SMALL testes
large breasts

58
Q

Treatment of Klinefelter

A

Testosterone replacement therapy TRT

59
Q

NP profile in Klinefelter

A 
IQ generally average
nonverbal > verbal
language skills deficit
dyslexia
ADHD, more I than C
slow processing
sensorimotor deficits
anxiety, depression, social withdrawal, behavioral
shy, emotionally sensitive, socially immature
60
Q

Fragile X syndrome

A

repetition in CGG trinucleotide sequence at Xq27.3
leading cause of inherited ID
most common single gene disorder leading to ASD!

normal lifespan

61
Q

Male or female more frequent in Fragile X

A

Males more affected

62
Q

Neuropathology of Fragile X

A

enlarged hippocampus, caudate nucleus, thalamus, amygdala (increased ASD and stereotypic tendencies)
reduction in size of cerebellar vermis
dysmorphia of cerebellar vermis and caudate nucleus (predict lower IQ)

63
Q

medical disorders with Fragile X

A

10-20% epilepsy mostly in males
- rhythmic theta waves, decreased and slower alpha

waves, slower background activity
- seizures usually resolve by adolescence

fragile X associated tremor/ataxia syndrome (FXTAS)
- progressive gait ataxia, intention tremor, parkinsonism

peripheral neuropathy, STM loss, EF
25-57% ASD in males

ADHD in 70-90% males, 30-50% females

80% males ID, 30% females ID (males lower IQ)

64
Q

progression of Fragile X

A

developmental delays first sign
large testicles during puberty
normal fertility

65
Q

Treatment of Fragile X

A

no cure

drugs that target glutamate receptors and GABA receptors

66
Q

NP results of Fragile X

A 
ASD
ADHD
ID (males worse, females mild)
poor math
VS
speech is echolalic, palilalia, perseveration, poor articulation, stutter
hyperarousal, approach withdrawal social behavior
poor eye contact (ASD Stuff)
EF, attention, processing speed
67
Q

Fragile X physical characteristics

A 
prominent ears
hyperextensive joints
flat feet
soft skin
macroorchidism
long face
68
Q

Turner Synrdome

A 
results from missing or abnormal second X chromosome
only in females
short stature
webbed neck
Cardiovascular malformation
congenital heart disease
kidney malformation
69
Q

neuropathology of Turner syndrome

A

decreased volume of parietal and occipital cortices
abnormal structure and function of amygdala, insula, anterior cingulate, ventromedial prefrontal cortices, orbitofrontal cortex
dysfunctional frontoparietal circuitry
agenesis or anatomical differences of corpus callosum

70
Q

medical disorders of Turner syndrome

A 
17-45% cardiovascular malformation
short stature 
osteoporosis, infertile
30% thyroid (hypothyroidism)
25% ADHD
45-55% math disability
reduced life expectancy due to cardiovascular malformation
71
Q

progression and presentation of Turner

A

developmental motor delays early

mosaicism (genetically different set of cells in body)

72
Q

treatment of Turner

A

estrogen, progesterone (growth hormone therapy)

73
Q

NP results of Turner Syndrome

A 
ADHD
NLD (spatial, math) 
*nonverbal deficits*
social skills
average IQ
significant verbal > non verbal
motor deficits
social cognition (socially immature, lack connectedness)
74
Q

Phenylketonuria (PKU)

A

mutation from PAH gene
identified through newborn screening blood test
autosomal recessive disorder
classified based on Phe level at dx
most people have mild phenotype
A birth defect that causes an amino acid called phenylalanine to build up in the body.

75
Q

Treatment of PKU

A

Phe-restricted diet

no cure

76
Q

Neuropathology of untreated PKU

A

hypomyelination and gliosis
progressive white matter degeneration
delay in development of cerebral cortex
diffuse cortical atrophy and reduced dendritic arborization

77
Q

Treated neuropathology of PKU

A

white matter abnormalities (t2 hyperintensity)

volume loss in cerebrum, corpus callosum, hippocampus, pons

78
Q

medical disorders with PKU

A

75% untreated have neurological dysfunction
5% of untreated have supranuclear motor disturbance
13-46% ADHD I
normal lifespan

79
Q

presentation of PKU

A 
untreated infants and babies - hypotonia, irritability, feeding problems, musty odor, psychomotor retardation
seizures in untreated babies 4-6 mos
cognitive decline 3-4 years
beh problems
OCD, self injury, tactile sensitivity
IQ below 50 if untreated
80
Q

important fact about PKU

A

early treatment makes a big difference

81
Q

NP results of PKU

A 
untreated IQ < 50
treated IQ normal
math problems
reading writing ok
VS deficits
EF deficits
processing speed related to PKU phenotype but not phe levels
adhd
82
Q

Prader Willi Syndrome

A

lack of paternally expressed genes in q11-13 region of chromosome 15

83
Q

Hallmark of Prader Willi

A 
hyperphagia - EXCESSIVE EATING
hypotonia
hypogonadism - not enough sex hormones
obesity
mild to mod ID
84
Q

Neuropathology of Prader Willi

A

structural neuroanatomical abnormality (pituitary gland, periventricular nucleus of hypothalamus…)

connectivity abnormality (FA studies, high trace value in left frontal white matter, left dorsomedial thalamus; low FA in posterior internal capsule, right frontal WM, corpus callosum)

abnormality in brain region related to eating (differences in amygdala and orbitofrontal cortex, delayed response to glucose ingestion in areas of satiety)

85
Q

medical disorders in Prader Willi Syndrome

A

IQ mild to mod ID
25% ASD
hypotonia life long
hypogonadism both male and female
lung disease, OSA, decrease O2 saturation
gastrointestinal complications (decreased saliva production, swallowing difficulties, unable to vomit)
obesity
short stature
diminished life span due to respiratory failure, choking

86
Q

presentation and course of prader willi syndrome

A

2 clinical phases

  • neonatal (birth to 3), hypotonia, hypereflexia, feeding problems, failure to thrive, delayed milestone, language
  • hyperphagic (onset 2-6 yrs), constant need for food
87
Q

Treatment for prader willi syndrome

A

no cure
early dx and intervention for dietary and behavioral problems
growth hormone tx
intervention on food restriction
SSRI for compulsive and injurious behavior

88
Q

NP results in Prader Willis syndrome

A 
IQ mild to mod ID
ASD
poor adaptive fx
non verbal IQ> verbal IQ
OCD, ritualistic tendencies
behavior problems
social deficits
psych (bipolar, mood)
89
Q

Angelman Syndrome

A 
lack of maternally expressed genes in q11-q13 region of chromosome 15
severe ID
ataxia
epilepsy
severe speech and language delays
repetitive, stereotyped behaviors
sensory seeking
happy and inappropriate laughter
hand flapping, waving (motor stereotypies)
90
Q

neuropathology of angelman syndrome

A

usually normal brain structure
EEG pattern
- symmetrical high voltage slow wave activity not associated with drowsiness
- very large amplitude slow activity in runs and more prominent in frontal region
- spike and sharp waves seen posteriorly and provoked by eye closure

background rhythm in ages 10+ slower than normal, focal spikes and intermittent and continuous triphasic delta activity over frontal region

91
Q

medical problems in Angelman syndrome

A

80-90% epilepsy
- tonic clonic, absence, complex partial, myoclonic, atonic, and tonic seizures
100% movement or balance disorder with ataxia of gait and tremulous limb movement
100% severe developmental delay, esp language and speech
sleep disorders
life span normal

92
Q

presentation and course in angelman syndrome

A

dev delay first noted in 6 months
slow progression
seizure onset 1-5 years, diminish during late childhood and adolescence and return in adulthood

93
Q

treatment of Angelman

A

no cure
multiple AED
speech therapy, use communicative device

94
Q

NP results in angelman syndrome

A

IMPAIRMENT in speech (absent or few words)
SEVERE ID
short attention span
movement disorder
abnormal muscle tone
behavioral WEIRD! (laughter inappropriate, smile, hand flaps, hypermotoric)
good eye contact, social skills ok
severe seizure cause temper tantrums, irritability

95
Q

palilalia

A

repetition of one’s own words

96
Q

phexiform neurofibroma

A

large, non encapsulated tumor that diffusely involves long nerve segments and has increased of becoming malignant

97
Q

schwannoma

A

benign nerve sheath tumor composed of schwann cells

98
Q

schwann cells

A

produce myelin sheath covering peripheral nerves

99
Q

karyotype

A

number and appearance of chromosome

100
Q

hamartoma

A

benign, focal malformation of tissue that has developed in a disorganized manner

101
Q

gynecomastia

A

male breast enlargement

102
Q

aneuploidy

A

abnormal no of chromosomes

103
Q

de novo mutation

A

genetic mutation that is present for the first time in a family member and not passed down by either parent

104
Q

ependymoma

A

tumor arising from ependyma

105
Q

ependyma

A

membrane lining the ventricular system

106
Q

glioma

A

tumor arising from glial cells in brain or spine

107
Q

facial features of angelman

A

wide mouth protruding tongue
deep set eyes
prominent chin

Elsa AACN (35 decks)

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